Transcript Introduction to Algorithm
Overview of I519 & Introduction to Bioinformatics
Structure of I519
Two classes and one lab each week Python, C (a little bit R) Textbook: Understanding Bioinformatics Homework assignments (~5 in total) Grading: – midterm exam (25%) + final exam (25%) + assignments (30%) + class project (15%) + attendance (5%) Course webpage: http://darwin.informatics.indiana.edu/col/courses/I519-12/
What’s bioinformatics
What’s Bioinformatics
"Bioinformatics is the field of science in which
biology
,
computer science
, and
information technology
merge into a single discipline. There are three important sub-disciplines within bioinformatics: the development of new algorithms and statistics with which to assess relationships among members of large data sets; the analysis and interpretation of various types of data including nucleotide and amino acid sequences, protein domains, and protein structures; and the development and implementation of tools that enable efficient access and management of different types of information.” (NCBI) "I do not think all biological computing is bioinformatics, e.g. mathematical modelling is not bioinformatics, even when connected with biology-related problems. In my opinion,
bioinformatics has to do with management and the subsequent use of biological information
, particular genetic information.” (Durbin)
What’s bioinformatics
Bioinformatics vs Computational Biology
Almost interchangeable Computational biology may be broader – Computational biology is an interdisciplinary field that applies the techniques of computer science, applied mathematics and statistics to address biological problems (wikipedia) – Includes bioinformatics
What’s bioinformatics
Impacts of Bioinformatics
On biological sciences (and medical sciences) – – Large scale experimental techniques Information growth On computational sciences – Biological has become a large source for new algorithmic and statistical problems!
What’s bioinformatics
Related Fields
Proteomics/genomics (metagenomics)/ comparative genomics/structural genomics Chemical informatics Health informatics/Biomedical informatics Complex systems Systems biology Biophysics Mathematical biology – tackles biological problems using methods that need not be numerical and need not be implemented in software or hardware
What’s bioinformatics
Bioinformatics Problems/Applications
Figure from “Bioinformatics dummies”
Biology primer
Eggs Cell divisions Multicullar organisms
Biology Primer
Figure 1-1
Molecular Biology of the Cell
Underlying the diversity of life is a striking unity: DNA is universal genetic language; Cells are the basic units of structure and function
Biology primer
Cells are the Basic Unit of Life
Cell Theory – – – – All organisms are made up of cells The cell is the
basic living unit
of organization for all organisms All cells come from pre-existing cells by division Cells contains hereditary information which is passed from cell to cell during cell division.
– – All cells are basically the same in chemical composition All energy flow (metabolism & biochemistry) of life occurs within cells Organisms can be of single cells or multiple cells (multicellular organisms) − − Most living organisms are single cells (e.g.,
E.coli
, Yeast) Multicellular organisms (e.g., human has more than 10 13 cells. Have no idea about this number? World population as of July 2008 is 6.684 billion, (1 billion = 10 9 )
Biology primer
Cell Structures
Animal cell structure http://hyperphysics.phy-astr.gsu.edu/hbase/biology/imgbio/cellhlabel.gif Prokaryotic cell structure http://micro.magnet.fsu.edu/cells/procaryotes/images/procaryote.jpg
Cell
Biology primer
Scale Down to the Atomic Level
Figure 9-1
Molecular Biology of the Cell
Figure 9-2
Biology primer
The Central Dogma
The flow of genetic information in cells is from DNA to RNA to protein. All cells, from bacteria to humans, express their genetic information in this way —a principle so fundamental that it is termed
the central dogma of molecular biology
.
Transcription DNA retrovirus RNA Translation Protein RNA virus
Biology primer
DNA and Replication
Figure 1-2
Molecular Biology of the Cell
, Fifth Edition
Biology primer
From DNA (to RNA) to Protein
Biology primer
The Genetic Code
Biology primer
Genome
Definition – Genome of an organism is its whole hereditary information and is encoded in the form of DNA (or, for some viruses, RNA) – Chromosome: structure composed of a long DNA and associated proteins; human has 46 chromosomes DNA sequences can be determined by various sequencing techniques Sequence first. Ask questions later – Cell. 2002 Oct 4;111(1):13-6
Biology primer
Three (Super)Kingdoms
Characteristic Archaea
Predominately multicellular DNA structure Cytoplasma is compartmentalized Introns are present in most genes Photosynthesis with chlorophyll Histone proteins present in cell No circular No No No Yes
Bacteria
No circular No
Eukaryote s
Yes linear Yes No Yes No Yes Yes Yes
Biology primer
Organisms at Pivotal Positions in the Tree of Life
Fly: 2000 Worm: 1998
E.coli
: 1997 Cell. 2002 Oct 4;111(1):13-6
Biology primer
Model Organisms
A
model organism
is a species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Genetic models (with short generation times, such as the fruit fly and nematode worm), experimental models, and genomic models, with
a pivotal position
in the tree of life
Biology primer
Escherichia coli
(
E. coli
)
A common gut bacterium, is the most widely used organism in
molecular genetics
.
Some strains of
E. coli
are capable of causing disease under certain conditions Different strains of
E. coli
have been extensively studied Whole genome of several
E. coli
strains was sequenced (e.g., K-12, O157:H7, HS)
Biology primer
The Genome of
E. coli
K-12
Circular DNA: a single, closed loop Protein-coding genes RNA genes The whole genome was sequenced in 1997 Total 4,639,221 bp.
Figure 1-29
Molecular Biology of the Cell
, Fifth Edition (© Garland Science 2008)
Biology primer
Caenorhabditis elegans
C. elegans
is a eukaryote (nematodes, or round worms) Has small genome (~97megabases) (whole genome sequencing, 1998)
C. elegans
is easy to maintain in the laboratory (in petri dishes) and has a fast and convenient life cycle. – – the life span is 2-3 weeks. tiny (1 mm in length) and
transparent
organism and the developmental pattern of all
959
of its somatic cells has been traced.
•
somatic cell
: any cell of a plant or animal other than cells of the germ line (from Greek
soma
, body)
Biology primer
Caenorhabditis elegans
(Cont.)
Discovery of the mechanism of RNA interference in
C. elegans
(1998) – Andrew Fire and Craig C. Mello shared the Nobel Prize in Physiology or Medicine in 2006 – Silencing was triggered efficiently by injected dsRNA, but weakly or not at all by sense or antisense single-stranded RNAs
Biology primer
Drosophila melanogaster
(fruit fly)
It has been used as a model organism for over 100 years, widely used to study genetic and development biology – – – Small and has a simple diet. Short life cycle: taking about two weeks Have large polytene chromosomes, whose barcode patterns of light and dark bands allow genes to be mapped accurately It was chosen in 1990 as one of the model organisms to be studied under the auspices of the federally funded Human Genome Project Whole genome sequenced in 2000 >10
Drosophila
genomes have been sequenced FlyBase: http://flybase.org/
Biology primer
Species Classification
Classification is arrangement of organisms into orderly groups based on their similarities Also known as taxonomy Provide accurate and uniform naming system
Biology primer
Linnaean System of Classification
Carolus Linnaeus (the “father of taxonomy”) -- the first widely accepted hierarchical scheme, which consists today of 7 categories (kingdom, phylum, class, order, family, genus, and species ) (not including domain) Species is the most basic unit of biological classification (means “kind” in Latin) – – Each species is different, and reproduces itself
faithfully
Heredity is a central part of the definition of life The Linnaean system uses two Latin name categories, genus and species, to designate each type of organism –
Salmonela saintpaul
(which caused the latest food-borne disease) – Capitalize the genus, but not the species; italicized in print
Biology primer
Homo sapiens
Domain: Eukaryotes K ing P hilip Kingdom: Matazon (many-celled animal) slits) Phylum: Chordata (characterized by a notochord, nerve cord, and gill (subphylum: Vertebrata) C ame Class: Mammalia (warm-blooded vertebrates) O ver Order: Primates F or Family: Hominidae G ooseberry Genus: Homo S oup Species: Sapiens http://www.ncbi.nlm.nih.gov/sites/entrez?db=taxonomy
Biology primer
Gene/Protein Family
A protein/gene family is a group of evolutionarily related proteins/genes Genes/proteins of the same family typically have similar functions (and structures for proteins) and with sequence similarity There are far more genes/proteins than the number of families —which shows the advantage of grouping genes/proteins into different families
Biology primer
Evolution of Genes
New genes are generated from preexisting genes – Intragenic mutation (modified by changes in DNA sequence – errors occurred in the process of DNA replication) – Gene duplication – two copies of genes may then diverge in the course of evolution – – Segment shuffling Horizontal transfer
More on what’s bioinformatics
Analysis of Gene/Protein Families – Key Problems in Bioinformatics
Homolog detection Alignment (the residual-level mapping among homologous genes/proteins) Application of the alignments – – – Detect the conserved residues – functional sites Prediction of protein structures Motif finding (cis-elements) Phylogeny Function annotation None of these problems have been solved!
More on what’s bioinformatics
Is Protein A Related/Similar to Protein B?
Sequence similarity (alignment!) Structure similarity (structural comparison) Co-expression (Microarray data analysis) Any types of correlation (operon-structure, etc) You will see this question again and again!
More on what’s bioinformatics
Guilty by Association
More on what’s bioinformatics
Computational Abstractions: Biological Sequences as Strings
DNA RNA Protein Phylotype DNA A string in a four-letter alphabet RNA Protein
More on what’s bioinformatics
Computational Abstractions: Networks (and Others) as Graphs
Protein-protein interaction network Protein structures presented as graphs Gene functions presented as graphs (Gene ontology) Metabolic pathways as graphs (directed)
More on what’s bioinformatics
Large Scale Data Analysis
Genome scale – genome, proteome, transcriptome Metagenome scale – Metagenome, metaprotome, metatranscriptome
More on what’s bioinformatics
More than Implementation
Find old/new biological problems
– Remember biology has become a large source for new algorithmic and statistical problem
Formulate as a computational problem
– –
Define inputs and outputs (though there are many paper work on well defined bioinformatics problems)
Apply existing algorithms and/or tools to solving your problem Develop new ones if necessary Implement your algorithms with appropriate programming language(s)
More on what’s bioinformatics
Where Can I Get the Biological Data?
Sequences – – NCBI genbank Swissprot Structures – PDB Genomes – – NCBI, IMG, GOLD Specialized genome resources • Ensembl: selected eukaryotic genomes.
Others – KEGG, SEED (biological pathways)
Dealing with Databases
Databases are the backbone of bioinformatics research Flat files were the first type of database; and are still used today Rational databases are good for searching purposes Databases can contain data and annotations of data – Primary and derived (secondary) data
Readings
Biology primer (available at the course website) Anything about Python and/or C (if you have no programming experience at all) What’s in the textbook?
– – – Chapter 1 ( The Nucleic Acid World) Chapter 2 (Protein Structure) Chapter 3 (Dealing With Databases)